1-26993995-T-C

Variant names:

• chr1-26993995-T-C
• rs1459872785
• NM_001013642.3:c.209T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001013642.3(TRNP1):​c.209T>C​(p.Leu70Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000873 in 1,144,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: TRNP1 NM_001013642.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0720
• Publications: 0 publications found

Genes affected

TRNP1 (HGNC:34348): (TMF1 regulated nuclear protein 1) Predicted to enable DNA binding activity. Predicted to be involved in several processes, including cerebellar cortex morphogenesis; neural precursor cell proliferation; and regulation of cell population proliferation. Predicted to be active in nucleus. Predicted to colocalize with euchromatin. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2420891).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001013642.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNP1	NM_001013642.3	MANE Select	c.209T>C	p.Leu70Pro	missense	Exon 1 of 2	NP_001013664.2	Q6NT89

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRNP1	ENST00000522111.3	TSL:1 MANE Select	c.209T>C	p.Leu70Pro	missense	Exon 1 of 2	ENSP00000429216.2	Q6NT89
	TRNP1	ENST00000531285.2	TSL:2	c.209T>C	p.Leu70Pro	missense	Exon 1 of 2	ENSP00000436467.2	H0YES3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.73e-7 AC: 1 AN: 1144954 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 551966

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 23340

American (AMR) AF: 0.00 AC: 0 AN: 9300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15786

East Asian (EAS) AF: 0.00 AC: 0 AN: 26998

South Asian (SAS) AF: 0.00 AC: 0 AN: 38426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25090

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3324

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 956624

Other (OTH) AF: 0.00 AC: 0 AN: 46066

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	23
DANN	Benign	0.88
DEOGEN2	Benign	0.038	T
Eigen	Benign	0.11
Eigen_PC	Benign	0.035
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.37	T
M_CAP	Pathogenic	0.33	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.072
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.084	T
Polyphen		0.99	D
Vest4		0.33
MutPred		0.34		Loss of helix (P = 0.0017)
MVP		0.40
ClinPred		0.94	D
GERP RS		1.4
PromoterAI		0.083	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.74
gMVP		0.35
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1459872785; hg19: chr1-27320486;